The invention relates to seven-carbon analogues of mannofuranose and, more particularly, to novel heptitol compounds and their syntheses from .delta.-lactones of heptonic acids. These novel heptitol compounds are useful inhibitors of glycosidases.
Polyhydroxylated nitrogen heterocycles constitute a major class of glycosidase inhibitors [Winchester and Fleet, Glycobiology 2, 199 (1992); G. Legler, Adv. Carbohydr. Chem. Biochem. 48, 319 (1990)] and may also provide clues to the nature of many carbohydrate recognition processes [Furui et al., Carbohydr. Res. 229 C1 (1992)]; glycosidase inhibition may be of value in the study of diabetes [Rhinehart et al., Biochem. Pharmacol. 39, 1537 (1990); Liu, J. Org. Chem. 52 4717 (1987)], cancer [Woynarowska et al., J., Anticancer Res. 12, 161 (1992); Liu et al., Tetrahedron Lett. 32, 719 (1991)] and some viral diseases [Jones and Jacob, Nature 330, 74 (1991); Taylor et al., AIDS 5, 693 (1991); Stephens et al., J. Virol. 65, 1114 (1991)]. Because of the potential chemotherapeutic applications of such materials, there is continuing interest int he synthesis of both monocyclic analogues [Lees and Whiteside, Bioorg. Chem. 20, 173 (1992); Hassan, Gass. Chim. Ital. 122, 7 (1992); Fairbanks et al., Tetrahedron 48, 3365 (1992)] and bicyclic analogues [Burgess and Henderson, Tetrahedron 48, 4045 (1992); St. Denis and Chan, J. Org. Chem. 57, 3078 (1992); Herczegh et al., Tetrahedron Lett. 33, 3133 (1992); Gradnig et al., Tetrahedron Lett. 32, 4489 (1991)]. In particular, the specific inhibition of individual N-linked glycoprotein processing .alpha.-mannosidases by nitrogen analogues of mannopyranose [Bischoff and Kornfeld, Biochem. Biophys. Res. Commun. 125, 324 (1984); Fuhrmann et al., Nature 307, 755 (1984)] and mannofuranose [de Gasperi et al., J. Biol. Chem. 267, 9706 (1992) may provide a useful anticancer strategy [White et al., Cancer. Commun. 3, 83 (1991); Olden et al., Pharmacol. Ther. 50, 285 (1991)].